The Lymphatic System and Immunity

• One hundred trillion microorganisms live on or inside the human body.
• Some of the millions of microorganisms living inside the body are necessary for health, while others can cause disease.
• Without an immune system, the body would be overrun by viruses and bacteria.
• The lymphatic and immune systems work together to protect the body.
• The immune system consists of cells that defend the body against disease, and most of these cells exist within the lymphatic system.

Lymphatic System

• Consists of lymphatic vessels, lymph, lymphatic tissue, and lymphatic organs.
• Lymphatic vessels cover the body similarly to blood vessels.
• Lymphatic organs and tissues include lymph nodes, thymus, tonsils, spleen, and red bone marrow.
• These tissues and organs produce immune cells.
• Lymphatic vessels are found in almost every tissue except for bone marrow, cartilage, and the central nervous system.
• Lymph is a clear, colorless fluid similar to plasma but with a lower protein content.
• Lymph originates in the tissues as the fluid left behind following capillary exchange.
• Lymph may contain lipids (after draining the small intestines), lymphocytes (after leaving the lymph nodes), hormones, bacteria, viruses, and cellular debris.
• Lymphatic vessels, also called lymphatic capillaries, have thin walls and valves to prevent backflow.
• Lymphatic vessel walls are formed by a thin layer of epithelial cells that overlap loosely, allowing gaps to exist between the cells.
• Lymphatic vessels carry fluid in one direction only: away from the tissues.

The Lymphatic System Functions

• Maintenance of fluid balance.
• Absorption of fat.
• Providing immunity.
• Fluid continually seeps out of capillaries into surrounding tissues.
• Capillaries reabsorb about 85% of the fluid, leaving about 15% behind.
• The lymphatic system absorbs this remaining fluid and returns it to the bloodstream; over the course of a day, this fluid can total as much as 4 liters.
• Specialized lymphatic vessels in the small intestines absorb fats and fat-soluble vitamins. Lymph nodes and other lymphatic organs filter lymph to remove microorganisms and foreign particles.
• Lymphatic vessels originate in tissue spaces as microscopic, blind-ended sacs within a bed of blood capillaries.
• Tissue fluid flows into the vessels through gaps between the cells, carrying bacteria and lymphocytes.
• Lymphatic vessels converge to form larger vessels and empty into lymph nodes, where immune cells phagocytize bacteria.
• The vessels continue to merge, forming lymphatic trunks that drain major regions of the body.
• The lymphatic trunks converge to form two collecting ducts: one near the right subclavian vein and one near the left subclavian vein.
• Lymph joins the bloodstream when the collecting ducts merge into the subclavian veins.
• The fluid moves passively through the lymphatic system, aided by rhythmic contractions of the lymphatic vessels.
• Valves within the vessels prevent backflow; contraction of skeletal muscles and respiration cause pressure changes that help propel lymph.
• The lymphatic system has two collecting ducts: the right lymphatic duct and the thoracic duct.
• The right lymphatic duct drains lymph for the upper right quadrant of the body into the right subclavian vein.
• The thoracic duct drains lymph from the rest of the body into the left subclavian vein.

Lymphatic Tissues and Organs

• Passages open to the outside of the body contain a scattering of lymphocytes throughout their mucosa linings.
• Lymphatic tissue exists in masses called lymphatic nodules.
• Peyer's patches are lymphatic nodules residing in the small intestines.
• Lymphatic organs, are well defined and include red bone marrow, the thymus, lymph nodes, the tonsils, and the spleen.
• Red bone marrow and the thymus are called primary lymphatic organs and provide a location for B and T lymphocytes to mature.
• Lymph nodes, tonsils, and spleen are termed as secondary lymphatic organs, and are where lymphocytes that have matured in either the red bone marrow or the thymus are stored.

Thymus

• Located in the mediastinum, the size varies with age.
• It is large in children but begins to shrink at about age 14.
• By adulthood, it is a fraction of its former size.
• It produces thymosin, a hormone that promotes the development of lymphocytes.
• Divided into lobules that extend inward from a fibrous outer capsule and consist of a dense outer cortex and a less dense medulla filled with T lymphocytes.
• Immature T lymphocytes travel from the red bone marrow to the outer cortex of the thymus, are protected from antigens in the blood, giving them a chance to divide and mature.
• The developing T lymphocytes migrate toward the inner medulla and encounter other lymphoid cells such as macrophages and dendritic cells.
• The process trains the new lymphocytes to distinguish between the cells of its host body and foreign cells then released into the bloodstream.

Lymph Nodes

• As lymph flows, it passes through multiple lymph nodes where the fluid slows to a trickle as the node removes pathogens and other foreign material.
• Lymph nodes are sites for final maturation of some types of lymphocytes and monocytes.
• The body contains hundreds of lymph nodes, shaped like a bean, some are tiny (1 mm long) while others are over an inch (25 mm).
• Lymph nodes remove 99% of the impurities in lymph before it returns to the bloodstream.
• Lymph nodes tend to occur in clusters in the neck, armpit, and groin.
• Cervical lymph nodes in the neck monitor lymph coming from the head and neck.
• Axillary lymph nodes, clustered in the armpit, receive lymph from the arm and breast.
• Inguinal lymph nodes occur in the groin, and they receive lymph from the legs.
• A fibrous capsule encloses each lymph node; connective tissue called trabeculae extend into the node, dividing it into compartments.
• The compartments, called cortical nodules, are filled with lymphocytes, and a less dense area at the center forms germinal centers that release lymphocytes when an infection is present.
• Sinuses lined with macrophages capable of phagocytosis separate the compartments, and lymph slowly flows through these sinuses in the process of being filtered.
• Several afferent lymphatic vessels channel fluid into a node, and after slowly filtering, lymph leaves through a single efferent lymphatic vessel.

Tonsils

• Masses of lymphoid tissue, form a protective circle at the back of the throat.
• Tonsils guard against pathogens entering the body through the nose or throat.
• There are three sets of tonsils: a single pharyngeal tonsil (adenoids), a pair of palatine tonsils in the oral cavity, and numerous lingual tonsils on the base of the tongue.
• Tonsils filter air flowing in through the nose and mouth, and white blood cells within the lymphoid tissue destroy any viruses or bacteria before they enter the body.
• When the palatine tonsils become infected by a virus or bacteria, they may swell and become inflamed, a condition known as tonsillitis.
• Symptoms of tonsillitis include a sore throat, painful swallowing, and fever, which usually resolves on its own when caused by a virus, but requires antibiotics when strep throat is the cause .
• Surgical removal of the tonsils is recommended only when tonsillitis resists treatment or repeatedly recurs.

Spleen

• About the size of a fist and is the body's largest lymphatic organ, residing in the upper left quadrant of the abdomen.
• Like lymph nodes, it is surrounded just like lymph nodes.
• Surrounded by a fibrous capsule; inward extensions of the capsule divide the spleen into compartments and contains two types of tissue: red pulp and white pulp.
• White pulp contains compact masses of lymphocytes and surrounds the arteries leading into each compartment.
• Red pulp exists along the edges of the compartments and consists of a network of erythrocyte-filled sinuses supported by reticular fibers and phagocytic cells.
• Blood collects in the venous sinuses after passing through the reticular fibers and returns to the heart through the veins.
• The spleen has many functions: immunity, destruction of old red blood cells, blood storage, and hematopoiesis.
• Lymphocytes and macrophages in the white pulp screen passing blood for foreign antigens while phagocytic cells in the sinuses ingest and destroy any microorganisms for immunity.
• Macrophages in the sinuses digest worn-out RBCs and imperfect platelets, recycling haemoglobin salvage the iron and globin and returning it to the bone marrow and liver for later use related to the destruction of old red blood cells.
• Spleen stores 20% to 30% of the body's platelets, and can, therefore, help stabilize blood volume; spleen also has blood storage and blood volume capability. The spleen produces red blood cells in the foetus; and throughout life, the spleen provides a location for monocytes and lymphocytes to mature, which relates to hematopoiesis.

Overview of the Immune System

• A person's survival depends on the body's ability to protect itself against viruses, bacteria, fungi, and protozoa.
• The body has three lines of defense: the first line of defense are external barriers, such as the skin and mucous membranes.
• The second line of defense is nonspecific immunity, including the production of phagocytic white blood cells and triggering inflammation and fever.
• Innate immunity mechanisms are present from birth, allowing the body to repel pathogens to which it has never been exposed.
• The third line of defense, known as specific immunity, occurs when the body retains a memory of a pathogen after defeating it, which allows them to quickly recognize it if exposed to the same pathogen in the future.

Nonspecific Immunity

• Protects against a broad range of pathogens, using external barriers, phagocytosis, antimicrobial proteins, natural killer cells, inflammation, and fever.
• The skin and mucous membranes provide the first line of defense against microorganisms. Consisting of tough protein, the skin also repels most pathogens, and is dry, lacking nutrients, and creates the acid mantle, a thin layer of acid produced by sweat.
• The mucous membranes lining the digestive, respiratory, urinary, and reproductive tracts produce mucus that physically traps pathogens.
• Mucus, tears, and saliva also contain lysozyme, an enzyme that destroys bacteria.
• If a pathogen makes its way past the skin or mucous membranes, it will immediately confront phagocytes.

Phagocytosis

• Phagocytes ingest and destroy microorganisms and other small particles.
• When a phagocyte encounters a microorganism, it sends out membrane projections called pseudopods.
• These pseudopods envelop the organism, forming a phagosome, which travels to the interior of the cell and fuses with a lysosome.
• A lysosome contains digestive enzymes which destroy the microorganism, and then waste products are released from the cell.

Types of Phagocytes

• The most important phagocytes are neutrophils and macrophages.
• Macrophages evolve from monocytes, migrate into connective tissues, and transform into larger macrophages.
• Macrophages are located in the alveolus of the lungs, the liver, nerve tissue, bone, and the spleen.
• Neutrophils travel to sites of infection after being summoned by a chemical released from inflamed cells (chemotaxis).
• The neutrophils anchor themselves to the inside of the blood capillary before enzymes are then used to digest a portion of the basement membrane.
• The neutrophil squeeze out of the vessel diapedesis and enters the inflamed tissue.

Antimicrobial Proteins

• Two types of proteins, interferons and the complement system, help provide nonspecific resistance against bacterial and viral invasion.

Interferons

• Some cells respond to viral invasion by producing a protein called interferon and releasing it to nearby cells which it then binds to surface receptors.
• This then triggers production of enzymes within the cells that would prevent the virus from replicating if it managed to invade.

Complement System

• Over 20 inactive proteins circulate in the bloodstream, forming an immune response to a bacteria, or antibodies against the bacteria and activating the complement.
• Once a complement reaction begins, it continues as a cascade of chemical reactions, with one complement protein activating the next.
• Complement aids the immune system by coating pathogens and stimulating inflammation via neutrophils through chemotaxis.
• The final proteins embed themselves into the bacterium's plasma membrane, punching a hole that lets fluid and sodium rush in, causing it to swell and burst.

Natural Killer Cells

• Continually roam the body, seeking pathogens or diseased cells.
• They recognize and destroy any foreign cells, including cancer cells, virus-infected cells, bacteria, and the cells of transplanted organs and tissues.
• NK cells use several methods to destroy the cells, mostly involving secretion of chemicals that causes the cell to die and break (lysis).

Inflammation

• Tissue injury produces inflammation.
• Inflammation stimulates the body's defense system to begin fighting the infection and instigates measures to contain the pathogen, cleaning up and repairing the tissue.
• Most of the phagocytes, mainly neutrophils, die during the process of fighting the infection.
• The dead cells pile up, along with tissue debris and fluid, to create pus (fluid), and when that accumulates in a tissue cavity, it's called an abscess.
• Redness, swelling, heat, and pain are the four classic signs of inflammation, and also facilitate healing.
• Swelling forces open the capillary valves to promote drainage.
• Hyperemia brings materials necessary for healing as heat increases the metabolic rate.
• Pain indicates an injury has occurred and to rest the area to allow healing.
• Suffix -itis denotes inflammation.

Fever

• An abnormal elevation of body temperature, also known as pyrexia or being febrile.
• Neutrophils and macrophages secrete a fever-producing substance called a pyrogen.
• The pyrogen stimulates the anterior hypothalamus to secrete prostaglandin E (PGE).
• PGE resets the body's set point for temperature, generating heat through shivering constriction of blood vessels.
• The temperature rises until it reaches its new set point, where it remains as long as the pathogen is present.
• Phagocytes stop producing the pyrogen and the body's set point for temperature returns to normal when the pathogen isn't a threat anymore, generating excess heat.

Specific Immunity

• Directed against a specific pathogen, the immune system retains a memory of the encounter and can recognize it, which is an important element for allowing to destroy the pathogen before symptoms even develop.
• The body employs cellular (cell mediated) immunity to destroy foreign cells or host cells that have become infected with a pathogen. The body also employs humoral (antibody-mediated) immunity which sends out antibodies to "mark” a pathogen for later destruction.

Natural Active Immunity

• Body routinely makes its own antibodies or T cells against a pathogen which an example would be building up a resistance for the measles by experiencing it.

Artificial Active Immunity

• Results when the body makes T cells and antibodies against a disease as a result of a vaccination and injecting a vaccine containing dead or weakened (attenuated) pathogens, the recipient's body produces an immune response, so there is no actually illness.

Natural Passive Immunity

• Results when a foetus acquires antibodies from the mother through the placenta or when a baby acquires them through breastfeeding.

Artificial Passive Immunity

• Obtaining serum from a person or animal that has produced antibodies against a certain pathogen and then injecting it into someone else.
• Typically used in emergencies for the treatment of rabies and botulism.

Lymphocytes Classes

• Natural killer cells
• T lymphocytes
• B lymphocytes

T Lymphocytes (T cells)

• Develop from stem cells in red bone marrow.

B Lymphocytes (B cells)

• Begin life as stem cells in red bone marrow.
• Unlike T cells, B cells remain in bone marrow until they are fully mature.
• T cells mature in the Thymus while B cells mature in the Bone marrow.
• Before the T cells fully have matured, they leave the bone marrow and travel to the thymus gland.
• T cells are immunocompetent (capable of recognizing antigens) as they exit the thymus and migrate to lymphatic organs and tissues throughout the body.

Antibodies

• Also known as immunoglobulins (Ig), consisting of chains of protein joined to form a Y or T shape, antibodies are gamma globulin proteins formed by B cells.
• Antibodies are found in plasma and body secretions.
• An antigen is any molecule that triggers an immune response and said to be antigenic.
• The immune system learns to distinguish between “self” and “non-self” cells before birth so that it attacks only those substances that aren't part of the body.

Antibodies Classes

• IgA: Populating mucous membranes in the intestines, respiratory tract, saliva, tears, and breast milk.
• IgD: Exists in the blood and may activate basophils and mast cells.
• IgE: Involved in allergic reactions.
• IgG: Is the primary antibody of the secondary immune response and the most abundant of all the immunoglobulins, comprising 80% of all circulating antibodies.
• IgM: Active in the primary immune response and agglutination of incompatible blood types.
• The end of each arm of the "Y" is uniquely shaped, allowing each antibody to combine with a specific antigen.

Cellular Immunity classes of T cells

• Cytotoxic T cells destroy pathogens, also called “killer” cells, which can't be confused with natural killer cells
• Helper T cells, which play a supportive role
• Memory T cells, which remember and are vigilant of the pathogen during future invasion

Immune Process

• When a phagocyte ingests an antigen.
• The phagocyte, called an antigen-presenting cell (APC), displays fragments of the antigen on its surface through a process of antigen presentation which spots the presence of a foreign antigen and a T cell binds to it.
• The T cell activates and begins dividing repeatedly and produce clones which then specialize to a specific branch such as a cytotoxic T cell, helper T, and memory T cell (will carry out the attacks), but some will also become memory T cells.
• The cytotoxic T cell delivers the antigens to the surface of the cell and kills the pathogen via toxins,.
• The helper T produces interleukin the chemical, which attracts neutrophils, natural killer, and macrophage.
• Some cytotoxic T cells and helper T cells become memory T cells after the attack and retain a memory of this particular pathogen.
• If a re-exposure occurs, these cells can launch a quick attack.

Humoral Immunity

• Differs from cellular immunity, as it focuses on pathogens outside the cell and doesn't destroy the antigen directly. However, it uses antibodies to mark them.
• The surface of a B cell contains thousands of receptors for a specific antigen, which binds to it when it comes along.
• The B cell engulfs the antigen, digests it, and displays fragments on its surface via a helper T cell that binds to the antigen and secretes interleukins that activate the B cell.
• The B cell begins to reproduce the antigen and has numerous clones.
• Some of these B cells then mostly become a plasma cell that secretes large numbers of antibodies, which makes the most memory cells.
• Antibodies bind to the antigen's attachment points, triggering agglutination and promotes the complement cascade ends with the destruction of the invading microorganism.

The Primary Response

• Occurs the first exposure to a particular antigen.
• The immune system must create B cells that will turn into differentiate into plasma cells that produce antibodies.
• This initial reaction called the primary response.
• The amount of time which can occur from three to six days between exposure and a rising blood antibody levels against that antigen.

The Secondary Response

• Once the attack is over and the antigen has been from the body, the B memory cells remain.
• The the number in antibodies decline, the antigen then invades again , this is called the secondary response. The body's ability to fight the infection (or attack) will occur quicker at only hours due to an increase of memory cells, resulting in fewer symptoms as opposed to the primary response that is is required for days and produces high symptoms for days.

Explore the primary functions of the thymus, tonsils, lymph nodes, and spleen within the lymphatic system. Understand their roles in immunity and the importance of considering surgical removal of lymphatic organs.